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M Simmonds

Publications and source records attributed to M Simmonds.

41 records · Page 3Linked to original sources
PubMed1986

Androgen priming and response to chemotherapy in advanced prostatic cancer.

A total of 67 patients with progressive stage D2 prostatic cancer refractory to orchiectomy was entered in a controlled clinical trial to test whether androgen priming enhances the efficacy of cytotoxic drugs. All patients were treated continuously with aminoglutethimide and hydrocortisone to lower adrenal androgen secretion and were given cyclic intravenous chemotherapy. In addition, the 34 patients randomized to the stimulation arm received fluoxymesterone for 3 days before and on the day of chemotherapy. There was 33 controls. The median duration of followup was 24 months. A modestly higher response rate (objective remission plus disease stabilization) was observed in the stimulation arm (85 versus 72 per cent, p less than 0.05) when the analysis was restricted to the evaluable patients. However, a larger fraction of unevaluable patients was present in the stimulation group (41 versus 16 per cent), mostly as a result of toxicity from fluoxymesterone, which prompted early discontinuation of treatment. Thus, when data analysis included all patients the response rate actually was slightly higher in the control than in the stimulation arm (60 versus 50 per cent, p not significant). No difference was observed in median duration of response (9 months in both groups) or over-all survival. Our data suggest that at least in those patients with advanced disease androgen priming does not seem to enhance significantly the antitumor effect of the combination of amino-glutethimide and chemotherapy, and is associated with significant toxicity. These largely negative results may be explained by the large number of hormone-resistant cells present in tumors that have become refractory to orchiectomy.

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Hormone stimulation and chemotherapy in advanced prostate cancer: interim analysis of an ongoing randomized trial.

We report here in the interim analysis of an ongoing randomized clinical trial designed to test whether androgen priming enhances tumor chemosensitivity in men with stage D prostate cancer refractory to orchiectomy. All patients are continuously treated with aminoglutethimide and hydrocortisone, to lower adrenal androgen secretion, and are given cyclic chemotherapy. Patients in the stimulation arm receive also the synthetic androgen, fluoxymesterone, for 3 days before and on the day of chemotherapy. Of 57 patients entered to date, 41 have received adequate treatment to be evaluable. Response to therapy (objective remissions + stabilizations of disease) occurred in 17 of 18 evaluable patients (94%) randomized to the stimulation arm, and in 16 of 23 evaluable patients (70%) in the control group (p less than 0.025). Duration of response was not significantly different in the two groups (median: 9 months in the stimulation and 12 months in the control arm). With 30% of the total of 57 patients still alive, survival is not significantly different in the stimulation (median: 13 months) and control arm (median: 16 months). As expected, patients who responded to treatment lived significantly longer than those who failed to benefit. Two episodes of reversible spinal cord compression occurred during androgen administration. (The risk of this serious side effect may be reduced by performing a screening myelogram to rule out subclinical spinal metastasis). Our preliminary data suggest that androgen priming may enhance the tumoricidal effect of cytotoxic drugs in advanced prostate cancer. The lack of improvement in duration of response and survival may be explained by the large fraction of hormone-independent cells probably present in patients with tumors refractory to orchiectomy.

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Hormone stimulation and chemotherapy in advanced prostate cancer: preliminary results of a prospective controlled clinical trial.

Preliminary evidence suggests that the sensitivity of endocrine-dependent neoplasms to chemotherapy may be enhanced by transient hormonal stimulation of tumor growth. To test this concept, we are conducting a prospective controlled trial in men with stage D2 prostate cancer who have relapsed following orchiectomy. All patients are continuously treated with aminoglutethimide and hydrocortisone to lower adrenal androgen secretion plus cyclic chemotherapy. Patients in the stimulation arm receive, in addition, the synthetic androgen fluoxymesterone for 3 days before and on the day of chemotherapy. Of 41 patients entered to date, 26 are evaluable. Twenty-one (81%) obtained either an objective remission or stabilization of disease with a mean duration of 9+ months and 10 patients still responding. Thus far, the response rate is similar in the control and stimulation groups. Androgen administration was associated with a rise in acid phosphatase and usually a modest flare of symptoms except for 2 patients who developed spinal cord compression. These preliminary data indicate that the combination of aminoglutethimide and chemotherapy has a potent antitumor effect on advanced prostate cancer refractory to orchiectomy. A large number of patients and a longer follow up are needed to assess whether transient androgen administration potentiates the effect of chemotherapy.

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